Agency to analyze research data on medications' effects

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WASHINGTON — The Food and Drug Administration has begun a preliminary inquiry into whether epilepsy drugs might increase the risk of suicidal behavior in some patients, particularly those who use them for psychiatric illnesses instead of seizure prevention.

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Prompted in part by an attorney’s claims against the leading anticonvulsant, Neurontin, the FDA last month asked makers of all epilepsy medicines to reanalyze research studies done with the drugs to see if there’s any evidence of increased suicide risk.

“I don’t think we have any suspicion yet that these drugs actually do that,” cautioned Dr. Robert Temple, FDA’s drug policy chief.

It’s the same type of analysis that FDA last year ordered for antidepressants amid controversy over their use by children and teenagers — and ultimately those drugs were linked to an increase in suicidal thoughts and actions in a small fraction, 2 percent to 3 percent, of young patients.

'Off-label' uses of particular interestIn addition to use by millions of people with epilepsy, anti-seizure drugs are becoming widely used to treat psychiatric illnesses such as bipolar disorder — also called manic depression — as well as pain and other conditions. Some epilepsy drugs have FDA approval for various other uses, while others are prescribed “off-label.”

There are reports of suicides among anti-convulsant users, most of them bipolar patients, Temple said. But without a close examination of research studies, it is impossible to tell whether a drug played a role or the disease itself was to blame, he explained, noting that between 10 and 20 percent of bipolar patients commit suicide.

But, “we are taking this matter very seriously,” Dr. Russell Katz, FDA’s chief of neurologic drugs, wrote New York attorney Andrew Finkelstein last week, a development first reported by The Boston Globe.

Finkelstein last summer filed a petition with the FDA asking that a black-box warning — the FDA’s toughest — about suicide be placed on Neurontin’s label. In the petition, Finkelstein cited 25 reports of suicides among Neurontin users from FDA’s own database.

FDA still is investigating the petition. So last month, Finkelstein sent the agency 258 reports he had collected of suicides by people apparently taking Neurontin. Finkelstein, who in fall 2003 aired a brief national television ad searching for such cases, has filed 72 lawsuits against Neurontin manufacturer Pfizer Inc.

Finkelstein also produced a 1992 FDA review of Neurontin that called depression a potential rare side effect.

Pfizer will comply with FDA’s request to reanalyze its studies, but patient data already submitted to the agency “shows no link between Neurontin and suicidal thoughts or behavior,” said spokesman Paul Fitzhenry.

Neurontin is approved to particularly hard-to-control epilepsy, a very serious condition.

The FDA gave Pfizer and manufacturers of all other epilepsy drugs six months to review their databases and report back to the agency.

The whole category of epilepsy drugs “is potentially very important” in treating other serious illnesses, “and we thought we ought to know this,” Temple said.